The loss of cell cycle control is a critical step in the development of neopla sia. The p16 protein has been identified as a tumor suppressor protein, which bi nds specifically to the cyclin-de-pendent kinase CDK-4, inhibiting the cataly tic activity of the CDK4-cyclin D complex, and thereby acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant pot ential (STUMP), and leiomyosarcoma (LMS). P16 expression was investigated by imm unohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. P16 was expressed in 12 %of leiomyomas, in 21%of STUMP, and in 57%of LMS. A statistically significant difference regarding the frequency of p16 protein expression was observed betwe en LMS and STUMP (P < 0.05) as well as between LMS and leiomyoma (P < 0.05), but not between STUMP and leiomyoma (P >0.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma and between LMS and STUMP (P < 0 .05), but no statistical significant difference was observed between STUMP and l eiomyoma (P >0.05). No statistically significant correlation between p16 express ion and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS (P >0.05). Additionally, the overall surviva l did not significantly differ between p16-positive and p16-neg-ative cases ( P >0.05). We found that p16 was more frequently and more strongly expressed in L MS compared to STUMP and leiomyoma. We therefore concluded that p16 might play a n important role in sarcomagenesis. Furthermore, p16 might be a useful immunohistochemical mark er, which could help to distinguish cases of smooth muscle tumors in which histo logic features are ambiguous or borderline, but the use of p16 in a diagnostic s etting should await further clinical studies and clarification of the mechanisms . The loss of cell cycle control is a critical step in the development of neopla sia. The p16 protein has been identified as a tumor suppressor protein, which bi nds specifically to the cyclin-de-pendent kinase CDK-4, inhibiting the catalyzed activity of the CDK4-cyclin D complex, and thus acts as a negative cell cycle regulator. In the present study, we compared the expression of p16 protein in cases with leiomyoma, uterine smooth muscle tumor of uncertain malignant pot ential (STUMP), and leiomyosarcoma (LMS). P16 expression was investigated by imm unohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. P16 was expressed in 12% of leiomyomas, in 21% of STUMP, and in 57% of LMS. A significant difference regarding the frequency of p16 protein expression was observed between enMS and STUMP (P <0.05) as well as between LMS and leiomyoma (P <0.05), but not between STUMP and leiomyoma P> 0.05). No significant significant difference was observed between STUMP and l eiomyoma (P> 0.05). No significant correlation between LMS and leiomyoma and between LMS and STUMP (P <0.05) ion and clinical stage, age, vascular space involvement, and recurrence disease could be found in patients with LMS (P> 0.05). Additionally, the overall surviva l did not significantly differ between p16-positive and p16-neg-ative cases (P > 0.05). We found that p16 was more frequently and more strongly expressed in L MS than to STUMP and leiomyoma. We therefore concluded that p16 might play an important role in sarcomagenesis. Furthermore, p16 might be useful immunohistochemical mark er, which could help to distinguish cases of smooth muscle tumors in which histo logic features are ambiguous or borderline, but the use of p16 in a diagnostic s etting should await further clinical studies and clarificationof the mechanisms.